Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study

Abstract

Aims: Clinical trials have demonstrated that a reduction in low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular (CV) events. This has, however, not yet been shown in a real-world setting. We aimed to investigate the association between LDL-C changes and statin intensity with prognosis after a myocardial infarction (MI).

Methods and results: Patients admitted with MI were followed for mortality and major CV events. Changes in LDL-C between the MI and a 6- to 10-week follow-up visit were analysed. The associations between quartiles of LDL-C change and statin intensity with outcomes were assessed using adjusted Cox regression analyses. A total of 40 607 patients were followed for a median of 3.78 years. The median change in LDL-C was a 1.20 mmol/L reduction. Patients with larger LDL-C reduction (1.85 mmol/L, 75th percentile) compared with a smaller reduction (0.36 mmol/L, 25th percentile) had lower hazard ratios (HR) for all outcomes (95% confidence interval): composite of CV mortality, MI, and ischaemic stroke 0.77 (0.70-0.84); all-cause mortality 0.71 (0.63-0.80); CV mortality 0.68 (0.57-0.81); MI 0.81 (0.73-0.91); ischaemic stroke 0.76 (0.62-0.93); heart failure hospitalization 0.73 (0.63-0.85), and coronary artery revascularization 0.86 (0.79-0.94). Patients with ≥50% LDL-C reduction using high-intensity statins at discharge had a lower incidence of all outcomes compared with those using a lower intensity statin.

Conclusions: Larger early LDL-C reduction and more intensive statin therapy after MI were associated with a reduced hazard of all CV outcomes and all-cause mortality. This supports clinical trial data suggesting that earlier lowering of LDL-C after an MI confers the greatest benefit.

Keywords: Cardiovascular mortality; Cardiovascular outcomes; LDL-C; Myocardial infarction; Secondary prevention; Statin.

Graphical abstract

Figure 1

Kaplan–Meier curves of the cumulative incidence rates by quartile low-density lipoprotein cholesterol (LDL-C) change from index event to the cardiac rehabilitation visit. Outcomes are assessed after the cardiac rehabilitation visit. Numbers at risk shown for MACE. MACE, major adverse cardiovascular event is the composite outcome of cardiovascular mortality, myocardial infarction, and ischaemic stroke.

Figure 2

Association between low-density lipoprotein cholesterol (LDL-C) change and outcomes. Cox proportional hazards analysis adjusted for clinical characteristics and established cardiovascular risk factors. Comparing the 75th percentile of low-density lipoprotein cholesterol reduction (1.85 mmol/L) with the 25th percentile (0.36 mmol/L) between index event and cardiac rehabilitation visit. Hazard ratio (HR) with 95% confidence interval (CI), E-value for hazard ratio, and confidence interval. MACE, major adverse cardiovascular event is the composite outcome of cardiovascular mortality, myocardial infarction, and ischaemic stroke. Coronary revascularization is defined as coronary artery bypass grafting or percutaneous coronary artery intervention.

Figure 3

Hazard ratio (HR) for the composite outcome MACE by change in low-density lipoprotein cholesterol (LDL-C,mmol/L) from index event to cardiac rehabilitation visit, adjusted for clinical characteristics, and established cardiovascular risk factors. Solid line: hazard ratio with 95% confidence interval (CI), shadowed area, in relation to low-density lipoprotein cholesterol change using restricted cubic splines with four knots. Vertical dotted lines: percentiles. X-axis presented on a linear scale. Population distribution in relation to change in low-density lipoprotein cholesterol below spline. MACE, major adverse cardiovascular event is the composite outcome of cardiovascular mortality, myocardial infarction, and ischaemic stroke.

Figure 4

Change in low-density lipoprotein cholesterol (LDL-C) and incidence rates. Data are shown for no reduction or an increase in low-density lipoprotein cholesterol (red), >0 but <50% reduction (blue), and ≥50% reduction (green) between index event and cardiac rehabilitation visit. Waterfall plot for change in low-density lipoprotein cholesterol (A) and concordant incidence rates per 1000 person-years with confidence intervals (B). MACE, major adverse cardiovascular event is the composite outcome of cardiovascular mortality, myocardial infarction, and ischaemic stroke. Major vascular event is the composite outcome of cardiovascular mortality, myocardial infarction, ischaemic stroke, and coronary revascularization (coronary artery bypass grafting or percutaneous coronary artery intervention).

Figure 5

Kaplan–Meier curves of the cumulative incidence rates by statin therapy intensity after cardiac rehabilitation visit and change in low-density lipoprotein cholesterol (LDL-C) from index event to cardiac rehabilitation visit . Data are shown for no reduction or an increase in low-density lipoprotein cholesterol, >0 but <50% reduction, and ≥50% reduction between index event and cardiac rehabilitation visit. Numbers at risk shown for myocardial infarction. MACE, major adverse cardiovascular event is the composite outcome of cardiovascular mortality, myocardial infarction, and ischaemic stroke.

Figure 6

Proportional reduction of event rates by degree of mean absolute low-density lipoprotein cholesterol (LDL-C, mmol/L) reduction . MACE, major adverse cardiovascular event is the composite outcome of cardiovascular mortality, myocardial infarction, and ischaemic stroke. Major vascular event is the composite outcome of cardiovascular mortality, myocardial infarction, ischaemic stroke, and coronary revascularization.